P1212: PERSONALIZED TREATMENT FOR ELDERLY PATIENTS WITH DIFFUSE LARGE B-CELL LYMPHOMA
Authors: H. Nukariya, K. Miura, H. Takahashi, M. Nakagawa, T. Hamada, S. Itho, T. Ichinohe, T. Endo, K. Kurihara, T. Koike, K. Iizuka, S. Ohtake, U. Yoshihito, N. Iriyama, Y. Hatta, H. Nakamura
Journal: HemaSphere (2022)

Background: The optimal dose intensity of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) for elderly patients with diffuse large B-cell lymphoma (DLBCL) has been controversial because the standard dose of CHOP is too toxic for some older adults. We previously developed Age, Comorbidity, Albumin (ACA) Index, a host-dependent prognostic model that can stratify the tolerability to R-CHOP treatment among patients aged ≥65-years with DLBCL. Aims: This study aimed to evaluate the efficacy of applying the ACA Index to real-world clinical practice. Methods: This was a retrospective, observational cohort study. Patients with DLBCL aged 65 years or older treated with R-CHOP with curative intent and written informed consent between January 2016 to February 2022 were included. The initial dose intensity (DI) was determined by International Prognostic Index (IPI), ACA Index, and organ functions by the team members of oncology physicians and pharmacists in our related institutions. ACA Index consisted of Age (>75 years), Comorbidity (Charlson Comorbidity Index score ≥3), and Albumin (<3.7 g/dL): patients were categorized into either Excellent (0 points), Good (1 point), Moderate (2 points), or Poor (3 points) group. Primary outcomes were treatment completion rate for full 6-cycles R-CHOP and estimated 2-year overall survival (OS). Secondary outcomes included initial DI; relative dose intensity (RDI) (i.e., regular-dose drugs delivered six cycles with just 21 days intervals equals 100%); and incidence of unplanned hospitalization, febrile neutropenia (FN), and treatment-related mortality (TRM). Results: A total of 158 patients were treated with R-CHOP during the study period but 20 patients were excluded because of poor records (N = 8), planned R-CHOP cycle number other than six (N = 7, e.g., abbreviated cycles plus radiation therapy), and treatment incompletion (N = 5). Thus, 138 patients with median 75 (range 65–91) years of age ware analyzed. Of these, 79 (57%) were high or high-intermediate risk in the IPI. Most patients had DLBCL not otherwise specified (N = 126), but patients with double-hit lymphoma (N = 5), intravascular lymphoma (N = 4), and transformed lymphoma (N = 3) were also included. In total, treatment discontinuation was observed in 27 patients due to adverse events (N = 16), progressive disease (N = 8), or patient’s request (N = 3). Consequently, treatment completion rate and 2-year OS for all patients were 80% and 76%, respectively. For ACA Index, 30, 45, 45, and 18 patients were categorized into Excellent, Good, Moderate, and Poor group, respectively. Treatment completion rates and 2-year OSs of these groups were 97%, 89%, 69%, and 61% (P = 0.0009) and 95%, 84%, 67%, and 46% (P = 0.0003), respectively. Among them, mean initial DIs were 94%, 83%, 71%, and 66% (P <0.0001) (Figure); mean RDIs were 89%, 75%, 59%, and 48% (P <0.0001); incidences of unplanned hospitalization were 10%, 16%, 22%, 44% (P = 0.03845); incidences of FN were 7%, 9%, 16%, and 28% (P = 0.1712); and incidences of TRM were 0%, 0%, 2%, and 17% (P = 0.0155). In an exploratory analysis for patients aged ≥80 years (N = 39%), treatment completion rate and 2-year OS were 72% and 69%, respectively, with mean initial DI and RDI of 62% and 53%, respectively. Image:Summary/Conclusion: Our risk-oriented, personalized strategy conferred an excellent outcome among non-selected, population-based elderly patients with DLBCL. The study results were comparable or even favorable compared to those of major clinical trials, in which one-size-fits-all strategies were adopted.